There is a compelling clinical need for functional biomaterials that are weight-bearing and actively remodel. For example, the treatment of tibial fractures is frequently complicated by delayed union and nonunion. The standard of care for treatment of displaced tibial plateau fractures (e.g., split and localized depression fractures) is internal fixation, which in some cases requires grafting with autologous bone to augment the internal fixation. Inadequate anatomical reduction of tibial plateau fractures has been associated with a high (30-80%) incidence of arthritic change in the knee. In order to eliminate the need for invasive internal fixation devices, the potential of calcium phosphate bone cements to maintain anatomical reduction of tibial plateau fractures has been investigated. In a retrospective analysis of 26 patients, 61% of patients treated with buttress plating and bone grafting experienced loss of reduction after one year compared to 23% of patients treated with calcium phosphate cement. Thus the bone cement preserved anatomical reduction, presumably due to its compressive strength exceeding that of the trabecular bone in the tibial plateau. However, the cement is not biofunctional, since it does not extensively remodel and is not replaced by new bone.
Osteonecrosis of the femoral head, which typically leads to hip replacement at a young age (<40 years) and afflicts ˜15,000 new patients each year, is another orthopaedic condition where treatment with functional biomaterials could improve patient outcomes. Hip replacement outcomes are not satisfactory, with failure rates ranging from 10-50% after five years. Non-invasive techniques, such as core decompression and nonvascularized bone grafting, have been used to treat early-stage osteonecrosis before collapse of the femoral head necessitates hip replacement. However, the results are varied with a 60-80% success rate, and outcomes are generally better in patients with very early-stage disease. Therefore, a non-invasive therapy accomplishing more predictable outcomes is desirable.
Injectable, functionally weight-bearing biomaterials that both possess initial mechanical strength comparable to host bone and maintain their initial strength while actively remodeling to form new bone would transform clinical management of a number of orthopaedic conditions. Functionally weight-bearing biomaterials for treatment of bone defects ideally possess five qualities: (1) biocompatibility of the material and its breakdown products, (2) injectability to enable less invasive application and fill irregularly shaped defects, (3) weight-bearing properties with strength comparable to that of healthy host bone at the defect site, (4) support of rapid cellular infiltration and remodeling at a rate that does not inhibit bone repair, and (5) delivery of biologics with proper release kinetics to accelerate bone formation and remodeling. Such a weight-bearing and/or biologically active biomaterial are not available.
Instead, commercially available injectable materials marketed as bone void fillers include calcium phosphate-based bone cements, which are osteoconductive, have compressive strengths comparable to trabecular bone (e.g., 5-40 MPa), and have fast setting times (<15 min). However, current calcium phosphates are subject to brittle fracture and graft migration, potentially leading to infections and requiring additional surgeries for repair or removal. To accelerate cellular infiltration and remodeling, implantable scaffolds with interconnected pores have been investigated, but interconnected pores have long been considered to significantly diminish the initial load-bearing properties of the materials, rendering them largely unsuitable for weight-bearing devices. Also, resorbable polymers have been blended with ceramics to yield weight-bearing composite implants that integrate and resorb, but these materials incorporate relatively low (e.g., 5-20 vol %) volumes of ceramic particles and the rate of remodeling is slow (<30% bony ingrowth after 4 years in a rabbit IM rod model) and scaled with the rate of polymer degradation. Furthermore, the incorporated particle generally have a size that is less than 20 μm.
Hence, there are remains a need for functional biomaterials that comprise synthetic allograft substitutes. There also remains a need for such composites that are injectable void fillers and/or putties, and that can have weight-bearing capabilities. Thus while currently available biomaterials address individually the requirements of a functional weight-bearing biomaterial, there is no device available that possesses more than three of the five key characteristics.